Interface circuit for use in a portable blood chemistry measuring apparatus

ABSTRACT

An interface circuit for use in a portable apparatus for measuring the electrochemical characteristics of a sample is disclosed. A disposable cartridge, including a plurality of interconnected flow chambers, houses a printed circuit board substrate upon which reference and indicating electrodes are formed. The electrodes are employed in the presence of chemical reagents to aid in the electrochemical determination of a sample undergoing analysis. Such a system provides a high source impedance signal. Interface circuitry is provided between the electrodes and measuring electronics which causes a controllable current loop to be formed through the physical contacts points between the electrodes and the measuring electronics so that low ohmic contact is established. The control circuitry for the current loop is isolated from the measuring circuitry so that measurements taken are not influenced by the current loop formation.

TECHNICAL FIELD

This invention relates to a portable apparatus to be used for accuratelymeasuring the electrochemical properties of a given sample. Morespecifically, the present invention relates to an apparatus formeasuring a blood gas panel, including pH value, of a whole blood sampleincluding interface circuitry for providing low ohmic contact betweenmeasuring electronics and a sampling electrode.

BACKGROUND OF THE INVENTION

The pH value of blood is a commonly monitored metabolic parameter andprovides a means for determining whether a proper physiologicalacid-base balance exists in the tested individual. A very delicate bloodpH balance is present in humans. Normal values for arterial blood rangefrom 7.25-7.45 with the lower and upper limits at which an individualcan survive being 7.00 and 7.70, respectively. When a cardiac or medicalarrest occurs, metabolic functions become anaerobic thus resulting inthe production of excess acids. This causes blood pH to lower.

As medical practitioners are aware, accurate and rapid determination ofwhole blood pH promotes the safe and effective resuscitation andtreatment of these arrest victims. Unfortunately, of the 640,000 cardiacarrests annually, 360,000 die before reaching the hospital partially dueto improper blood pH levels which are incapable of being monitoredon-site due to the prohibitory size of the current pH analyzers.Moreover, current analyzers are complex pieces of machinery requiringoperation by skilled laboratory technicians. For example, calibration ofthese systems does not occur automatically. An electrolyte must beintroduced into the measuring cassette by some form of mechanicalmanipulation before calibration can occur.

Additionally, the determination of pH on these systems is based on theglass electrode, as described by Cremer in 1906. These electrodes arecomposed of two half cells, one which generates a reference potentialand the other being constructed of a glass membrane. These electrodessuffer from several shortcomings including the need for constantcalibration as a result of half cell current drift, degradation of themembrane surface by cleaning solutions used to remove accumulatedprotein deposits, and the requirement of a large sample size.

U.S. Pat. No. 4,340,457 to Kater, discloses the use of metal electrodesto be used for in vivo potassium determination which can be stored wetin electrochemical contact. These electrodes, however, require furthermanipulation and hydration before calibration can occur. Further, thecalibration liquid must be removed before use in taking the actualmeasurement.

U.S. Pat. Nos. 3,742,594 to Kleinberg, 3,926,766 to Niedrach et al and4,561,963 to Owen et al, disclose the use of metal electrodes forelectrochemical determination of various bodily fluids. All of thesesystems utilize wire probes, as opposed to planar structures which arenot conducive to the use of chemical pastes as thin films such as thoseused in the present invention. Further, these electrodes require liquidtight seals making their manufacture very difficult.

U.S. Pat. No. 4,545,382 to Higgins et al discloses a metal electrodecoated with a film of glucose oxidase. This system, however, utilizes asingle sensor electrode, and is incapable of effecting a pH measurement.

U.S. Pat. Nos. 4,272,245 and 4,342,964 to Diamond et al disclose anapparatus and method for measuring the pH value of a blood sample whichutilizes metal electrodes. This method, however, requires the presenceof a liquid electrolyte used to calibrate the system and to provide anelectrolytic bridge between the sample and the reference electrodewithin a cassette. Calibration does not occur automatically but, rather,the solution is introduced into the cassette by mechanical manipulation.Such solutions are heat sensitive and therefore must be storedrefrigerated. The electrolyte-containing cassette must be heated to 37degrees celsius prior to use as pH is a function of the temperature ofthe sample to be measured. After heating, the cassette has a shelf lifeof approximately one hour. A pH measurement using this method thereforerequires proper treatment of the cassette containing the electrolytebefore an accurate value can be determined. This can create unwanteddelay in emergency situations. Additionally, the apparatus is designedto accommodate only one cassette at a time. Subsequent samples must beloaded into the machine manually and the user must wait a given amountof time before an accurate measurement can be made, thus causing anadditional delay in critical circumstances. Further, a reading can onlybe taken when the cassette is in an upright position. Moreover, themeasuring instrument which embodies the subject matter of these patentsis large, table-top size, and requires a line source of power in orderto perform the heating, measuring and other functions.

A further difficulty is encountered in blood gas measurement systems.Where an electrode system is used in which a measurement circuit ispositioned in and out of contact with the electrode system, good, lowohmic contact is difficult to achieve. This is because the electrodesprovide signals having a very large source resistance. As such, there isinsufficient current flow to produce good low ohmic contact between theelectrode system and the measurement circuit. The physics of this isthat even with sliding gold contact surfaces there is always a surfacelayer which will provide some insulation. When working at very highcircuit impedances, this layer is sufficient to degrade voltagemeasurement.

OBJECTS AND SUMMARY OF THE INVENTION

Accordingly, it is an object of the present invention to provide aninexpensive, portable apparatus for accurately measuring and reporting ablood gas panel, including pH levels, in whole blood to be used byparamedics, nurses, physicians and other practitioners.

It is another object of this invention to provide a system for pHmeasurement whereby the user need never come in direct contact with theblood sample to be measured.

It is a further object of the subject invention to permit a blood gaspanel, including pH measurement, to be taken from a minimal quantity ofblood.

It is another object of the present invention to provide a system for pHmeasurement which permits an insitu calibration without mechanicalmanipulation and which requires no special storage nor heat treatment ofthe chemicals or sample prior to measurement.

It is still another object of the present invention to provide aninterface between the electrode system and the measurement circuitrywhich will permit good ohmic contact to be obtained there between.

These and other objects are accomplished by way of a portable apparatusdesigned to accept a multiplicity of cartridges, each containing ameasuring structure. One of the cartridges is then advanced intoposition within the apparatus. The apparatus then goes through a seriesof operational tests upon the positioned cartridge. The measuringstructure is automatically calibrated and a temperature measurement istaken. If all readings are within the normal range, the apparatusprompts the user and a sample to be measured or analyzed is introducedinto the cartridge. The cartridge is ejected following the determinationof a blood gas panel, such as a pH value. In this way, the user neednever come in contact with the blood sample being measured.

According to another aspect of the present invention, a blood sample isintroduced into a disposable cartridge and drawn through a series ofinterconnected flow chambers including a sample chamber. The chambersdownstream of the sample chambers act as overflow chambers to take upexcess of the sample. Positioned within the sample chamber is asubstrate upon which pH measuring means and thermal sensing means aredisposed. It is a feature of this invention that the contents of thecartridge need not be heated prior to pH determination since a liquidelectrolyte is not used and since the thermal sensing means functions tomeasure the actual temperature in-situ, at the time of calibration andof analysis, and automatically corrects the reading to a standardtemperature, as preferred by medical personnel.

pH determination is accomplished by an electrode system which has astructure that is adaptable for use in determination of other bloodparameters in a blood gas panel such as O₂, CO₂, etc. A multiplicity ofelectrodes, each adapted for measuring a different gas, can therefore beused to measure a full blood gas panel. In accordance with the presentinvention, the electrodes are substantially miniature planar structures.As such, all the necessary electrodes may be positioned within a singlesample measuring chamber. The electrode circuit system is formed on adouble-sided printed circuit board substrate. One side of the printedcircuit board includes a plurality of gold-coated pads for makingelectrical contact between the substrate and a compatible pH analyzer.Copper traces on the other side of the circuit board form miniature,substantially planar structures upon which are formed an indicating anda reference electrode. The indicating electrode is coated with a metalor metal-metal oxide combination capable of developing a stablepotential when in contact with an electrolyte.

In the preferred embodiment, the reference electrode is formed from asuitable metal-metal halide combination such that a stable potential isestablished when in contact with an electrolyte.

The electrodes are further coated with a thin film of a chemical pastethereby providing electrochemical contact between the indicating andreference electrodes. Alternatively, the chemical coating can be appliedin two steps such that a thin film of paste is coated around thereference electrode and an indicator paste is coated as a thin film tosurround the indicating electrode and the chemical paste in contact withthe reference electrode.

An important aspect of the present invention is that the chemical pastesperform a dual function; that is the pastes are employed in both thecalibration of the electrodes and in the measurement of the sample. Inother words, unlike other electrode systems, the electrodes of thepresent invention need not have their calibrating medium cleared fromthem prior to actual measurement operation.

It is a feature of this invention that the formation of the electrodesas planar structures allows for the use of thin films of chemical andindicating pastes. The chemical compositions of the pastes permitstorage of the electrodes in electrochemical contact and thus automaticcalibration can take place immediately prior to sample injection withoutany prior hydration or user manipulation. Further, the cartridgecontaining the above described electrode structure can be stored at roomtemperature and need not be refrigerated to preserve the reactivity ofthe chemicals.

In the present invention, good ohmic contact is achieved between theelectrode structure and the measurement electronics by way of means forgenerating isolated and non isolated currents which will flow throughthe electrode contact pads.

Further objects and advantages of the subject invention will becomeapparent from the following detailed description when taken inconjunction with the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of the portable apparatus according to thepresent invention.

FIG. 2 is an exploded view of the preferred embodiment of a disposablecartridge according to the instant invention.

FIG. 3 is a top plan view of the disposable cartridge according to theinstant invention.

FIG. 4 is a cross sectional view along the lines 4--4 of FIG. 3.

FIG. 5 is a cross sectional view along the lines 5--5 of FIG. 3.

FIG. 6 is a fragmentary cross sectional view along lines 6--6 of FIG. 3.

FIG. 7 is a perspective view of the preferred embodiment of the printedcircuit board substrate of the present invention.

FIG. 8 is a bottom plan view of the preferred embodiment of the printedcircuit board substrate of the instant invention.

FIG. 9 is a cross sectional view along the lines 9--9 of FIG. 7.

FIG. 10 is a schematic of the electrode, thermal sensor and fill sensorcircuitry, and associated measurement electronics.

FIG. 11 is a cross sectional plan view of the portable pH measuringapparatus according to the present invention.

FIG. 12 is a cut away end view along the lines 12--12 of FIG. 11.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring now to FIG. 1, a portable pH measuring apparatus 10 isillustrated. The pH measuring apparatus 10 includes a shell 11 whichhouses a cartridge bay 12 designed to receive a plurality of cartridges.The plurality of cartridges are loaded into apparatus 10 by way ofU-shaped clip 14. New cartridges 16 are manually loaded onto theU-shaped clip 14. Clip 14 possesses longitudinal lips 15 to secure thecartridges 16. Subsequent cartridges 16 are loaded onto the clip 14until it is either full or the desired number of cartridges have beenloaded. A sleeve 17 provides a finger grip so that the clip 14 can bemanually loaded into the cartridge bay 12. The sleeve 17 also acts as abarrier to ensure proper insertion of the new cartridges within the pHmeasuring apparatus 10. Sleeve 17 is somewhat larger in overalldimensions than the cartridge bay 12.

More specifically, as illustrated in FIGS. 11 and 12, as the clip 14enters the cartridge bay 12, it contacts a cartridge follower block 74.A constant force spring 72, such as model no. CF015-0050 from AssociatedSpring, Cerritos, Calif. is inserted and pinned at one end to thecartridge follower block 74. The other end of spring 72 is anchored tothe shell 11 so that spring 72 becomes loaded as the follower block 74is forced backwards along channel 73 by the entering clip 14. When thesleeve 17 contacts the outer edges of the shell 11, the clip 14 isremoved and discarded. As clip 14 is withdrawn, a reciprocatingprojection 90, which was depressed downward by the cartridge clip 14,lifts and engages with a capturing groove 76 of the cartridge 16. Thecartridges 16 are now in place within the cartridge bay 12 andmeasurement can commence. The cartridge 16 which is in the measurementposition below a sample input port 13, has an electrical contactestablished between it and the apparatus 10.

The apparatus 10 further includes a cartridge counting mechanism (notshown) which keeps track of the number of cartridges present in thecartridge bay 12. This number is provided to the user by way of a visualdisplay described herein below.

The portable pH measuring apparatus 10 is turned on via an on/off button(not shown) located on the apparatus 10. The apparatus 10 then conductsa series of automatic, self-diagnostic tests to ensure its properoperation. If everything is in order, the measuring structures arecalibrated automatically, without any operator manipulation, asdescribed in further detail below, and a temperature measurement istaken. If the measurements taken during the self-diagnostic tests areoutside the normal range, a readout 22, FIG. 1, preferably a liquidcrystal display, will instruct the user to discard the cartridge and anew cartridge can be inserted and the above steps repeated.

When the cartridge is validated, the values are stored in memory and thereadout 22 will so inform the user and a sample can then be insertedinto the cartridge 16. As shown in FIGS. 1 and 4, the needle of asyringe 18 containing a blood sample to be measured is then passedthrough a shell hole (sample input port 13) and then inserted through atop seal 20 in the cartridge 16 and the blood sample is then dispensedinto the cartridge 16.

A venous selection button 21, and arterial selection button 25, locatedon the face of the apparatus 10, allows the user to set the instrumentfor use with arterial or venous blood samples. In operation, thereadings are calculated as arterial and a conversion factor is appliedif the instrument is in the venous mode. The pH is determinedpotentiometrically, the temperature correction is calculated and a valuecorresponding to the pH of the measured sample is corrected to 37degrees and displayed on the readout 22.

Referring now to FIGS. 11 and 12, the used cartridge can be ejectedafter a reading has been taken by pushing a spring actuated button 82located on the apparatus 10. This causes a substantially L-shaped member84 to rotate about a pin 81 in a clockwise direction thus drawing a pushrod 86 towards the distal end of the apparatus 10. The drawing motion ofthe rod 86 applies a pulling force on "V"-shaped spring 79. This causesopposing projection 80 to pivot about a pin toward the proximate end ofthe shell 11. The user then pushes sideways on cartridge bay door 24 toengage notch 78 with opposing projection 80. This operates to maintaincartridge bay door 24 in an open position while the used cartridge isbeing ejected.

When the rod 86 is drawn towards the distal end of the apparatus 10, abell crank 88 located in the proximal end of the apparatus 10 rotates ina clockwise direction about a pin 83. This motion forces thereciprocating projection 90 downward, thus freeing the used cartridge.The spring mounted cartridge follower block 74, which is biased byconstant force spring 72 to apply force on the cartridges, is thenpermitted to move forward to forcefully eject the used cartridge out ofthe apparatus 10. This permits the used cartridge to be disposed ofdirectly into a biohazard bin.

A bellcrank 82A is attached to another reciprocating projection 92 bymeans of a spring 87. As bellcrank 82A is rotated counterclockwise bymovement of the push rod 86, the spring 87 pushes the projection 92 inan upward direction. This upward movement serves two purposes. First,the projection 92 applies a frictional force to the exiting cartridge sothat the used cartridge is ejected in a controlled fashion.Additionally, the projection 92 captures the next cartridge by engagingwith the capturing groove 76 on that cartridge. This prevents its exit.Once push button 82 is released, opposing projection 80 will rotate in acounterclockwise direction to release the closed position. Spring 85,which was loaded when cartridge bay door 24 was opened, supplies thereturn force to close the door.

When the eject button 82 is released, the ejection mechanism returns toits resting position as illustrated in FIG. 11. The reciprocatingprojection 92 moves downward and at the same time the otherreciprocating projection 90 moves upward. Projection 90 thus exchangesposition with projection 92 and catches the opposing groove 76 thuslocking it into position so that a new pH measurement can be taken. Thismethod of ejecting and advancing the cartridges eliminates the need foruser contact with the blood-containing cartridge.

FIG. 12 is a cross sectional view of the invention taken along lines12--12 in FIG. 11. There it can be seen that the cartridge 16, which isto receive a blood sample, is positioned in alignment with a sampleinput port 13. As shown, in this alignment, needle guideway 34 ispositioned beneath sample input port 13.

As further illustrated in FIGS. 2-6, the disposable cartridge 16includes a box-shaped housing 27 preferably composed of a staticconductive material such as a carbon filled polymer, to bleed off thestatic charge that might be accumulated on the cartridge to theatmosphere. The top seal 20 of the disposable cartridge 16 is composedof a resilient material, such as but not limited to a silicone polymer.The top seal 20 operates in conjunction with a terminal air bleed port28 to maintain a fluid-tight environment within the cartridge 16.

The terminal air bleed port 28 contains a submicron filter 30,preferably hydrophobic in nature. The submicron filter 30 is designed toprovide a pressure differential between the cartridge 16 and the outsideenvironment such that under static conditions the pressure differentialthreshold across the filter 30 is high and impedes the free flow of airin and out of the cartridge 16. When the sample is injected, airpressure builds. Thus, as the sample to be measured enters the cartridge16, air within the cartridge is displaced and forced out of the terminalair bleed port 28 causing a directional flow of the sample through aseries of interconnected flow chambers, housed within cartridge 16.These form a flow path, indicated by arrows 32.

More specifically, a needle 18, attached to a syringe 19 containing theblood sample to be measured, enters a longitudinally extending needleguideway 34, and pierces the top seal 20. As illustrated in FIGS. 4-6,the needle guideway 34 is bounded by walls 36, formed in top seal 20,which serve as guides to direct the needle towards the sample chamber38. The needle guideway 34 is offset from a measuring structure 40 andthermal sensor 42 which are disposed on a printed circuit boardsubstrate 44. The printed circuit board substrate 44 forms the bottomboundary of the sample chamber 38, See FIG. 2, and is approximately ofthe dimensions 0.625 inches×0.625 inches×0.0625 inches. Thisconfiguration prevents the needle 18 from contacting and damaging themeasuring structure 40 and thermal sensor 42. The circuit boardsubstrate 44 also provides a barrier which prevents the needle fromexiting the cartridge 16 through the bottom. Circuit board substrate 44is held in place relative to the bottom of box-shaped housing 27 by wayof fingers 29. See FIGS. 4 and 5. In the manufacturing process, thesefingers 29 are initially formed as part of the side walls of thebox-shaped housing 27, and then heat-deformed after the circuit boardsubstrate 44 is positioned against the bottom of the box-shaped housing27. A gasket 31 is positioned between the circuit board substrate andthe bottom of box-shaped housing 27 to form a seal.

The blood sample is dispensed from the syringe 19 after the needle 18has passed through the needle guideway 34 and into the sample chamber38. Blood then flows into the sample chamber 38. The sample chamber 38has a depth dimension that is positioned along the longitudinal axis ofthe needle guideway 34. The sample chamber 38 extends transversely andoutwardly with respect to its depth dimension. A capillary sizedintermediate air bleed port 46 is located so that the measuring andthermal sensing structures are positioned between the point where theblood sample enters the sample chamber 38 and the location of theintermediate air bleed port 46. This positioning of the intermediate airbleed port 46 aids in the prevention of air bubble formation. Further,the intermediate air bleed port 46 allows air trapped in the samplechamber 38 to be exhausted so that blood will flow into the samplechamber 38 and over the measuring structure 40 and the thermal sensor42. In this manner, the directional flow of blood onto the measuringstructure 40 is achieved, and the sample chamber 38 filled at anyattitude between 0 degrees horizontal to 90 degrees vertical in spite ofthe high surface tension of blood relative to the force of gravity.

When the sample chamber 38 is full, blood flows through an overflow port50, FIGS. 3 and 6, over a fill sensor 52, and into one of a series ofoverflow chambers 54 located substantially opposite the intermediate airbleed port 46. The presence of the overflow chambers 54 is desireablebecause only a minute quantity of blood is needed for pH determinationand this small amount cannot be controllably dispensed by the user.

Since the size of the intermediate air bleed port 46 is very small incomparison to the overflow chambers 54, blood is held in the air bleedport 46 by capillary action and the high surface tension of the blood.Blood fills the overflow chambers 54 after the sample chamber 38 hasbeen completely filled.

The overflow chambers 54 form a series of interconnected flow channelswhich surround the needle guideway 34 and sample chamber 38. When one ofthe overflow chambers 54 is full, blood spills into a pathway connectingthe full chamber to an upstream overflow chamber.

This configuration of the interconnected flow chambers 32 permits use ofthe cartridge 16 in the apparatus 10 where the apparatus 10 ispositioned in a continuous attitude of angles from horizontal tovertical. Thus, a reading can be taken when the apparatus 10 ishand-held and changing positions.

When the presence of a sample is detected by the fill sensor 52, theelectronics of the apparatus 10 emits an audible signal and cuts thefill sensor 52 out of a common circuit shared by the measuring structure40, the thermal sensor 42, and the fill sensor 52, thus allowing pHmeasurement to take place. Specifically, the impedance between the fillsensor 52 and the ground point 56B is measured by injecting a current 53into point 56D, through the blood, and out of point 56B, and thenmeasuring the voltage 55 which results between the points. See FIG. 10.When blood is present between the ground point 56B and the fill sensor52, the measured impedance will be substantially low as compared to whenthe blood has not reached the level of the fill sensor 52. When bloodhas not yet reached this level, the impedance will be essentiallyinfinity. There will be a difference in magnitude of impedance of atleast 2 orders of magnitude when blood is present versus when blood isabsent.

Referring now to FIGS. 7-9, pH measurement is taken via the measuringstructure 40 formed on a double sided printed circuit board substrate44. The printed circuit board substrate 44 can be made from a reinforcedpolymer, such as an FR4 type phenolic epoxy. Other suitable materialsinclude: reinforced paper, various molded polymers, reinforced or filledmultipolymers, or any of the other standard types of printed circuitboard substrates. These materials need not be smoothly planar and may beof a type such as three dimensional molded plastic, such as polyethersulfone. The printed circuit board includes a layer of copper on bothsides which is etched by well known techniques to form electricalcontact pads 56 on the outer surface and electrode base structures andthermal sensor mounting pads on the inner surface of the printed circuitboard substrate 44.

In the preferred embodiment as illustrated in FIG. 8, four electricalcontact pads 56A through 56D, with plated-through holes 58A through 58D,and 59, are present. A wire 52 is connected to contact pad 56D by way offeed-through 58D. Electrical contact pad 56B is longer than the othersto ensure proper sequencing of power and ground to the measuringstructure 40. The electrical contact pads 56A through 56D are designedto make contact with spring tensioned pads 91, FIG. 12, disposed in theportable pH apparatus 10 so that all the measurements can be effected.

The measuring structure 40, comprises an indicating electrode 40B and areference electrode 40A, and is formed on the inner surface of theprinted circuit board substrate 44. The underlying structure for theseelectrodes are pads of copper 60 formed by standard printed circuitboard etching techniques. The use of printed circuit board technology asa foundation for the measuring means 40 provides a highly reproducible,low cost and high volume manufacturing technique.

Referring to FIG. 9, the copper pad 60 for the indicating electrode 40Bis coated on all surfaces with a metal 62, preferably silver, thenfurther coated with gold or platinum, or platinum group metals, or anyother metal capable of developing a stable potential when in contactwith an electrolyte. Alternatively, the indicating electrode can beformed from metal-metal oxide combination such as antimony layered oversilver and further coated with antimony oxide. U.S. Pat. Nos. 3,742,594to Kleinberg and 3,926,766 to Niedrach et al disclose the manner inwhich antimony electrodes can be formed.

The copper pad 60 for the reference electrode 40A is coated with ametal-metal halide combination such that a stable potential isestablished when the reference electrode 40A is in contact with anelectrolyte. In the preferred embodiment, the reference electrode 40A iscoated on all surfaces with silver 64 and further coated with silverchloride formed by anodic oxidation in dilute hydrochloric acid.Alternatively, the reference electrode 40A can consist of a calomel cellwhich is well known in the art.

In the preferred embodiment, the manufacturing sequence is as follows:(1) formation of the copper traces, including electrical contact traceson the outer surface, and electrode base structures and thermal sensorpads on the inner surface; (2) silver coating of all copper traces; and(3) gold over-coating of the silver-coated indicating electrodestructure and the remaining conductive structures on the printed circuitboard substrate 44, that is everything except the reference electrodestructure.

As illustrated in FIG. 9, the measuring structure 40 is coated with athin film of a chemical paste 68 including a pH indicator, such asquinhydrone, a standard pH 7 buffer, and a binder. It is to beunderstood that, although a pH 7 buffer has been used in the presentexample, other pH buffer values can be used as well. If anantimony-antimony oxide cell is used, no additional indicator isnecessary.

In an alternative embodiment of the present invention, the paste iscoated in two steps such that a chemical paste, without a pH indicator,is first coated as a thin film to surround the reference electrode 40Aand an indicator paste with a pH indicator is formed as a thin film tosurround both the indicating electrode 40B and the chemical paste thatis in contact with the reference electrode.

The overall construction of the measuring structure 40 allows for theuse of a very small quantity of sample, as little as a few drops, sinceonly the surface of the measuring structure 40 need be exposed to thesample to be measured. Further, the nature of the chemicals usedobviates the need for refrigeration to preserve the reactivity of thereagents and allows for automatic instrument calibration since theelectrodes are stored in electrochemical contact.

The pH of the sample solution is determined by measuring the differencein electrical potential established between the reference electrode 40Aand the indicating electrode 40B in the following manner. Thequinhydrone is derived from an equimolar mixture of hydroquinone andquinone, which form an oxidation-reduction couple sensitive to pH.Hydroquinone is the reduced form of quinone. As known in the art, when amixture of the two are in contact with an inert metal such as that usedto form the indicator electrode 40B, the reaction can proceed in eitherdirection as illustrated below. ##STR1## The driving force of thereaction depends on the acidity and thus the pH of the solution incontact with the redox couple. Thus, a half-cell emf can be measured bythe indicating electrode 40B when the redox couple is in contact withthe chemical and indicator pastes described above versus the referenceelectrode 40A. This potential is compared to the potential establishedby the indicator and the reference electrodes when in contact with thepastes, prior to introduction of the sample, and a suitable mathematicalformula is then used to determine the sample's pH value and stored in amicroprocessor (not shown) in the portable pH apparatus 10. Referring toFIG. 10, the electrode potential is taken by measuring the voltagebetween pads 56A and 56B in the following manner. An instrumentationamplifier 204 is configured as a voltage follower, and its noninvertinginput is coupled to contact pad 56A. As described hereinbelow, anisolated current loop is formed using the collector and emitter ofphototransistor 200 in contact with contact pad 56A at two spaced apartpoints, 201A and 201B. This forms what can be viewed as microwelds.Then, the isolated current loop is turned off. The instrumentationamplifier 204, connected to the emitter of phototransistor 200, can thentake a measurement 206 of the electrode potential through a low ohmiccontact. As can be seen from FIG. 10, this measurement is referenced toground contact pad 56B.

Since pH is a function of temperature, the value determined above mustbe further corrected for any temperature variation. This is accomplishedby the thermal sensor 42 which is located near the measuring structure40 and disposed on the inner surface of the printed circuit boardsubstrate 44 as illustrated in FIG. 4. The thermal sensor 42 ispreferably constructed from a surface mount, or die, silicon thermistor.Due to its close proximity to the measuring structure 40, the thermalsensor 42 is able to accurately determine the pre-exposed temperature ofthe measuring structure 40, and the temperature of the blood sampleundergoing measurement once the blood sample has been introduced intothe sample chamber 38. The thermal sensor 42 is connected to a commoncontact point 56B which is shared by the indicating electrode 40B. SeeFIG. 10. A potential and temperature measurement can be takensequentially and any variation in temperature can be corrected for bymultiplying the obtained pH value by a blood temperature coefficientprogrammed in the microprocessor (not shown) within the portable pHanalyzer 10. Similar corrections are made for each of the electrodes.Referring to FIG. 10, temperature is measured by injecting a current, I,between the thermal sensor contact 56C and the ground contact 56B andmeasuring the voltage, V, across the two contacts. The resistance, R,can then be determined according to the well known equation R=V/I.

As discussed briefly earlier in this disclosure, one of the problemsencountered with high source impedance measuring circuits, such as theelectrode system of the present invention, is that good ohmic contactbetween the electrodes and the measuring electronics is difficult toachieve. As can be seen in FIG. 12, as a cartridge 16 is advanced intoposition to receive a blood sample, pads 56A through 56D come intocontact with corresponding spring loaded fingers 91. In the preferredembodiment of the present invention, the pads 56A through 56D and thespring loaded fingers 91 are gold plated. However, even with the use ofsliding gold contact surfaces, as will be present when cartridge 16 isadvanced into position, there still remains a surface layer which willprovide some insulation. With the high source impedance signals that aresought to be measured, this layer of insulation is sufficient to degradethe measurement being taken.

In the present invention, the electrochemical cell parametersencountered makes it preferable that the measurement electronics have aninput impedance of greater than 10¹² ohms, and that leakage currents becontrolled to be less than 10⁻¹² amps. The output impedance of the cellitself can be on the order of 10¹¹ ohms. As a consequence, capacitiveloading at the measurement electronics should be strictly avoided.

As new cartridges 16 are positioned for receiving a blood sample, goodohmic contact can be achieved between the electrodes and the measurementelectronics by running sufficient current through what is essentially adry contact so that the contacts will in a sense microweld and provide alow resistance. It is to be understood that in "practice," electricalcontact to the electrode cell is made by way of a contact pad. Themeasurement contacts are brought into physical contact with thesecontact pads and measure the voltage present at the contact pads.

Thus, in order to achieve good, low ohmic contact, a current should begenerated which will flow from one of a pair of measurement contactsinto and through the contact pad and back into the other of the contactpads. This should be isolated from all of the rest of the electronics.The generation of such current should be associated with but isolatedfrom a control function which times or controls the value of the currentused. In other words, an action-at-a-distance coupling is desireable. Itis desireable to be able to control the current and turn it off so thatonce a good contact is made, there is not a voltage drop across thecontact which might be caused by the generating current. Such a voltagedrop would lead to unpredictable voltage offsets in the measurement.

There are several possible mechanisms for causing such current to flowin a predictable manner. For example, thermocouples could be placed oneither side of the two contacts. One of them could be remotely heated.Unfortunately, the unusual metals involved could present uncontrolledthermoelectric currents. Further, such a system has a slow responsetime. Once heated, the thermocouple would have to cool and be maintainedat the same temperature as the other thermocouple.

Another example is that the secondary of a transformer could be placedin the current loop. Current in the secondary could be induced bycurrent in the primary of the transformer. While this configurationwould be workable, the primary drive circuitry would be somewhat complexand the direction of current flow is not easily controlled.

As can be seen from FIG. 10, in the preferred embodiment of the presentinvention, a photo-diode or photo-transistor 200 is placed in thecurrent loop. Light from an LED 202 or other source is turned on tocause current to flow in the photo-diode or photo transistor. Thecollector of transistor 200 is physically contacted with pad 56A at onepoint, contacting structure 201A and the emitter of transistor 200 isphysically contacted with pad 56A at a different spaced apart point,contacting structure 201B. The driver circuit for the LED is a simplecommon emitter stage (not shown) which can use a PNP transistor, such asdevice number 2N2907. An optical isolator, such as device number 4N35,manufactured by Hewlett Packard of Palo Alto, Calif. is readilyavailable, and contains both a photo-transistor and an LED. With such astructure, the current flow is controllable in both magnitude anddirection, and can be readily turned off. Further, there are nosignificant thermoelectric currents. In the preferred embodiment of thepresent invention, a current of approximately 50 to 100 microamps iscaused to flow through transistor 200. In general, a current of two tothree times the magnitude of the current sought to be measured should beused to form these low ohmic contacts.

It is now readily apparent that the instant invention provides a meansfor accurately determining all parameters associated with in-situ pHmeasurement of whole blood. Since the described apparatus is portableand requires a very small sample size, measurements can easily be takenin emergency situations by ambulance attendants and the like. The userneed never come in contact with the blood sample being measured thuseliminating the dangers associated with such contact. It should beunderstood that while the subject invention has been disclosed withreference to a preferred embodiment, various alternatives to the uniqueconcepts described herein may be employed in practicing the presentinvention. Thus, although the measuring structures and chemistry of thepresent invention have been disclosed with reference to pH measurement,alternative uses, such as the measurement of other blood gas parameters,can be envisioned using the present system. It is intended that thefollowing claims define the invention, and that the structure within thescope of these claims and their equivalents be covered thereby.

What is claimed is:
 1. An apparatus for measuring a signal having a highsource impedance of the type in which the signal to be measured ispresented across a pair of contacts, and a measuring circuit is placedin physical contact with the pair of contacts, comprisinginterface meanshaving a plurality of contacting structures which can be placed inphysical contact with and at spaced apart points on at least a first oneof the pair of contacts for circulating a current through the first oneof the pair of contacts by way of the plurality of contactingstructures, wherein the circulating current flows out of one of theplurality of contacting structures, through the first one of the pair ofcontacts, and into another of the plurality of contacting structures,and further wherein the magnitude of the circulated circuit is selectedto cause a low ohmic contact to be developed between the plurality ofcontacting structures and the first one of the pair of contacts; meansfor measuring the signal between one of the plurality of contactingstructures and the other of the pair of contacts.
 2. The apparatus ofclaim 1, wherein the interface means comprisesphototransistor meanshaving as collector coupled to at least one of the contacting structuresand an emitter coupled to at least a different one of the contactingstructures for generating the current to be circulated; and means inoptical communication with the phototransistor for driving thephototransistor means so that the driving means are electricallyisolated from the phototransistor means.
 3. The apparatus of claim 1,wherein the measuring means includes means having a high impedance inputcoupled to one of the contacting structures for electronically bufferingand amplifying the high impedance signal appearing across the pair ofcontacts with respect to the other one of the pair of contacts.
 4. Theapparatus of claim 2, wherein the phototransistor means has a base, andfurther wherein the driving means includesa light emitting diodeoptically coupled to the base of the phototransistor means; and meanscoupled to the light emitting diode for driving the light emitting diodemeans.
 5. An apparatus for measuring a high impedance signal which ispresented across a pair of contacts, comprisinga phototransistor havinga base, a collector which can be placed in physical contact with one ofthe pair of contacts, and an emitter which can be placed in physicalcontact with the one of the pair of contacts at a point spaced apartfrom the collector; a light source in optical communication with thebase of the phototransistor which is operable to drive thephototransistor at a circulating current level that is sufficient tocause microwelds to be developed at the points of physical contactbetween the collector and emitter and the one of the pair of contacts,so that a low ohmic path is provided therebetween; and means formeasuring the signal between one of the pair of contacts and either thecollector or emitter of the phototransistor.